Felbinac (4-biphenylacetic acid) is an active metabolite of fenbufen which is a non-steroidal anti-inflammatory analgesic agent and also is a drug having high anti-inflammatory analgesic activity. Felbinac has a problem in which oral administration causes side effects in the digestive system, resulting in gastrointestinal injury. Therefore, use of felbinac as a percutaneous absorption preparation has been investigated. To date, external preparations such as a gel preparation and a liquid preparation are commercially available.
In the preparation forms of gel preparation and liquid preparation, quantitative administration is difficult, and bioavailability is low. Further, the preparations have a problem such as adhesion to clothes.
In order to overcome the problems of such gel preparation and liquid preparation, an aqueous patch (cataplasm) and an oily patch (plaster), which contains various anti-inflammatory analgesic agents in addition to felbinac, have been developed. In particular, the oily patch (plaster) becomes the mainstream of a non-steroidal anti-inflammatory analgesic patch since it does not have a cool touch when applied. A preparation having a rubber-based base and a tackifying resin in combination is generally used.
A non-steroidal anti-inflammatory analgesic patch usually contains various additives to improve the percutaneous absorption properties of a drug. In particular, L-menthol is useful as a solvent of felbinac, and is an additive which is often contained in commercially available felbinac-containing patches. However, it is widely known that L-menthol reacts with felbinac to produce an L-menthol ester as a degradation product. Therefore, the presence of L-menthol is a cause of deterioration of felbinac stability in the patch.
Irritating odor produced by sublimation of L-menthol is offensive to many people. For this reason, the market has a high demand for a patch preparation which does not contain L-menthol or prevents L-menthol odor, in fact.
Further, in order to enhance the percutaneous absorption properties of felbinac, addition of a percutaneous absorption enhancer such as crotamiton, fatty acids, fatty acid esters, monoterpenes, polyhydric alcohols, and pyrrolidones has been investigated.
For example, Patent Document 1 has proposed a felbinac-containing patch which has an adhesive layer containing crotamiton having a high solubilizing ability for felbinac as an essential ingredient. However, the patch has a problem of decrease of adhesion with time since crotamiton tends to bleed out onto the surface of the adhesive layer.
Further, Patent Document 2 discloses a felbinac-containing anti-inflammatory analgesic tape which contains a styrene-isoprene-styrene block copolymer as an adhesive and L-menthol and various absorption enhancers in combination. However, L-menthol in the tape may react with felbinac to produce a degradation product as described above. In addition, addition of L-menthol and the absorption enhancer in combination may make physical properties of a base deteriorate and cause skin irritation.
Patent Document 3 also discloses a felbinac-containing patch which contains terpene, sebacate ester, and an alkyl glyceryl ether. However, similarly to Patent Document 2, Patent Document 3 leaves something to be desired in drug stability, physical properties of a base, and skin irritation.
Further, patches containing various percutaneous absorption enhancers, such as a felbinac patch containing N-methyl-2-pyrrolidone and polyethylene glycol in combination (Patent Document 4) and a patch containing hydrogenated oil (Patent Document 5) have been investigated. However, a percutaneous absorption preparation having high percutaneous absorption properties and safety of a drug and excellent drug stability has not been found.
On the other hand, there have been attempts to enhance the percutaneous absorption properties of a drug by a means other than a method for adding a percutaneous absorption enhancer.
For example, Patent Document 6 discloses a water-containing plaster, in which an adhesive base containing a styrene-isoprene-styrene block copolymer as a main component contains lanolin and the lanolin holds water.
The technique disclosed in Patent Document 6 is an attempt to increase the solubility of felbinac by the water content in the preparation, resulting in improvement of percutaneous absorption properties. However, the production process is complicated by incorporating the water content in an oily patch. Further, the physical properties of the preparation during storage may deteriorate.
In addition, the plaster has a problem of slightly lower percutaneous absorption properties as compared with a plaster using a percutaneous absorption enhancer.
Patent Document 7 has proposed a patch. The patch does not contain crotamiton. In the patch, felbinac is uniformly dispersed in an adhesive base containing a styrene-isoprene-styrene block copolymer as a main base and a rosin-based resin.
However, the rosin-based resin in the patch acts as a skin sensitization ingredient. Blending of the rosin-based resin is known to be undesirable. Skin sensitization is one type of delayed-type hypersensitivity reaction, and a phenomenon in which chemicals cause excessive immune reactions to produce irritation to the skin.